Citations

Earlier studies [P. J. Westervelt, J. Acoust. Soc. Am. 29, 199–203, 934–935 (1957)] of the mutual nonlinear interaction of two plane waves of sound with each other are extended to include the viscous effect. The viscous effect is considered both from the equations of motion and the equation of state of the medium. An analytical solution to the lowest-order scattering process is obtained if the viscous effect of second order and higher can be neglected.

Purpose Surgical resection of liver-only metastases from colorectal cancer has undergone extensive evaluation and review. The use of neoadjuvant chemotherapy to improve the likelihood of resection in disease that is not optimally resectable has not been as well studied. Patients and Methods Patients with liver-only metastases from colorectal cancer deemed not optimally resectable by a surgeon with expertise in liver surgery received fluorouracil, leucovorin, and oxaliplatin (FOLFOX4). Patients were periodically reassessed for resectability. Surgical response was classified as completely resectable (S-CR), partially resectable (S-PR), or unresectable (S-UR). Study design specified the accrual of 39 patients, with two or more S-CRs considered evidence of promising activity with respect to increasing the S-CR rate. Results Forty-two of 44 patients were assessable for this analysis. Twenty-five patients (60%) had tumor reduction by serial imaging. Seventeen patients (40%) underwent surgery (S-CR, n = 14; S-PR, n = 1; and S-UR, n = 2) after a median of 6 months of chemotherapy. With a median postsurgical follow-up of 22 months (range, 13 to 32 months), 11 recurrences have occurred in the 15 S-CR and S-PR patients. Median survival time was 26 months. Conclusion Our data suggest that FOLFOX4 has a high response rate (complete response, partial response, or reduction) in patients with liver-only metastases from colorectal cancer, allowing for successful resection of disease in a portion of patients initially not judged to be optimally resectable. However, a high recurrence rate after surgery was observed, which, in 73% of patients, involved the liver. Further trials are indicated based on the promising results observed in this trial.

Frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) is caused by mutations in the gene encoding the microtubule-associated protein, tau. Some FTDP-17 mutations affect exon 10 splicing. To correct aberrant exon 10 splicing while retaining endogenous transcriptional control, we evaluated the feasibility of using spliceosome-mediated RNA trans-splicing (SMaRT) to reprogram tau mRNA. We designed a pre-trans-splicing molecule containing human tau exons 10 to 13 and a binding domain complementary to the 3′ end of tau intron 9. A minigene comprising tau exons 9, 10, and 11 and minimal flanking intronic sequences was used as a target. RT-PCR analysis of SH-SY5Y cells or COS cells cotransfected with a minigene and a pre-trans-splicing molecule using primers to opposite sides of the predicted splice junction generated products containing exons 9 to 13. Sequencing of the chimeric products showed that an exact exon 9–exon 10 junction had been created, thus demonstrating that tau RNA can be reprogrammed by trans-splicing. Furthermore, by using the same paradigm with a minigene containing full-length intronic sequences, we show that cis-splicing exclusion of exon 10 can be by-passed by trans-splicing and that conversion of exon 10 – tau RNA into exon 10 + tau RNA could be achieved with ≈34% efficiency. Our results demonstrate that an alternatively spliced exon can be replaced by trans-splicing and open the way to novel therapeutic applications of SMaRT for tauopathies and other disorders linked to aberrant alternative splicing.

This investigation examined listener transcriptions of phrases produced by speakers with mild to severe hypokinetic dysarthria to examine individual strategies for the identification of word boundaries in connected speech. It was hypothesized that the most efficient listeners would use syllabic strength information to guide their parsing of the continuous acoustic stream. Six-hundred transcribed phrases (10 listeners ×60 phrases) were coded independently by two judges to identify (1) correct word transcriptions, (2) evidence of accurate lexical parsing, regardless of exact word identification, and (3) the proportions of accurate parsing of strong and weak syllable word onsets. Linear regression analysis of the group data revealed that correct segmentation of strong syllable word onsets predicted listener performance on segmenting weak syllable word onsets [R=0.805, F(1,29)=51.440, p<0.001]. Despite a wide range of listener performance on ``words correct,'' individual strategies for perceptual segmentation were evident only in the transcriptions for the most severe speaker. In this case, the poorest listeners exhibited disproportionate difficulty with the segmentation weak syllable word onsets. Results suggest that a listener's ability to use syllabic strength information in lexical parsing determines, in part, their ability to recognize word onsets. [Work supported by NIDCD, NIH.]

Acoustic radiation pressure exerted by an arbitrary acoustic wave in a three-dimensional lossy medium is calculated by extending an indirect approach developed by Chu and Apfel [B-T. Chu and R. E. Apfel, ‘‘Acoustic radiation pressure produced by a beam of sound,’’ J. Acoust. Soc. Am. 72, 1673–1687 (1982)]. Without appealing to the detailed solutions of equations governing fluid motion, a general analytic expression for the radiation pressure in lossy media with arbitrary waves is obtained. When an infinite lossy medium is considered, the expression states that the radiation pressure, to the lowest order of approximation (i.e., second order), is equal to corresponding total energy density. For a special class of confined spaces, the expression leads to a rather general formula for the radiation pressure, in which the radiation pressure is given in terms of various energy densities in the field. Furthermore, a relationship among these energy densities is generalized to the case of lossy media, which enables one to compute the radiation pressure in the class of spaces with the knowledge of the first-order perturbation solution only.

Distortion product otoacoustic emission (DPOAE) input/output functions were measured at nine f2 frequencies ranging from 500 to 8000 Hz in 210 normal-hearing and hearing-impaired subjects. In a companion paper [Stover et al., J. Acoust. Soc. Am. 100, 956–967 (1996)], L1−L2 was held constant at 10 dB, and L2 was varied from 65 to 10 dB SPL in 5-dB steps. Based upon analyses using clinical decision theory, it was demonstrated that DPOAE amplitudes for 65/55 dB SPL primaries (L1/L2) and DPOAE thresholds resulted in the greatest separation between normal and impaired ears. In this paper, the data for these two conditions were recast as cumulative distributions, which not only describe the extent of overlap between normal and impaired distributions, but also provide the measured value (i.e., the specific DPOAE amplitude or threshold) for any combination of hit and false alarm rates. From these distributions, confidence limits were constructed for both DPOAE amplitude and threshold to determine the degree of certainty with which any measured response could be assigned to either the normal or impaired population. For these analyses, DPOAE measurements were divided into three categories (a) response properties that would be unlikely to come from normal ears, (b) response properties that would be unlikely to come from impaired ears, and (c) response properties for which hearing status was uncertain. Based upon DPOAE amplitude measurements, the region of uncertainty, defined between the 95 percentile for impaired ears and the 5 percentile for normal ears, was relatively narrow for f2 frequencies ranging from 707 to 4000 Hz. For DPOAE thresholds, this region was relatively narrow for f2 frequencies ranging from 1414 to 4000 Hz.

This study examined the effect of primary stimulus level on the ability of distortion product otoacoustic emission (DPOAE) measurements to separate normal-hearing from hearing-impaired ears. Complete I/O functions were obtained for nine f2 frequencies on 210 people approximately evenly divided between normal hearing and hearing impaired. Clinical decision theory was used to assess both DPOAE amplitudes and DPOAE threshold as diagnostic indicators of hearing status. Moderate level primary stimuli elicited responses that separated normal from impaired better than either lower level or higher level stimuli. The two populations were differentiated for all frequencies above 500 Hz by DPOAE amplitude, given primary levels, L1 and L2, of 65 and 55 dB SPL. DPOAE threshold performed equally well, but threshold ambiguity in noise and longer testing times make it a less suitable DPOAE measure to use diagnostically.

Modern commercial medical ultrasound instruments are capable of obtaining up to 40 real-time, two-dimensional images per second. One of the most difficult organs to evaluate with ultrasound is the heart. The heart is a complex organ that achieves its pumping function through cyclic motion of its chambers and valves. Computerized visualization of the heart is being developed to aid in training and to provide comprehensible images of this complex organ to the patient, the surgeon, and the researcher. To obtain the required data, the two-dimensional imaging plane of an ultrasound instrument is scanned through the heart from the surface of the chest, or more commonly, from within the esophagus. Sequences of digitized two-dimensional images taken at incremental positions through the heart are gated with the cardiac cycle and assembled by computer programs into volumetric images. Visualization methods of filtering, segmentation, and rendering are used to produce comprehensible, data dense, three-dimensional images of the heart. Sequences of the three-dimensional images obtained at sequential points through the cardiac cycle produce what are called ‘‘four’’-dimensional images. Mathematical projections of elements of these images onto selected two-dimensional planes can be recorded on videotape to produce movies of the structure or function of interest at various angles of view. Metrics such as distance, area, volume, or speed can be used on these data to produce quantitative measurements.

Theories on acoustic radiation pressure associated with plane acoustic waves and lossless media have been examined extensively. The radiation pressure produced by a non-plane wave in a lossy unbounded medium was analyzed. The distinction between Lagrangian and Eulerian pressure was used to clarify the understanding of radiation pressure. The radiation pressure exerted on a perfectly absorbing pointwise target by an arbitrary acoustic wave in an unbounded lossy medium was then considered. By using an indirect approach developed in Chu and Apfel [B.-T. Chu and R. E. Apfel, 1673–1687 (1982)], the radiation pressure was analyzed without appealing to the detailed solutions of the governing fluid dynamic equations. It was shown that even in lossy media with arbitrary waves, the radiation pressure experienced by a pointwise target is equal to the Langevin pressure which is the time average energy density at that point. The radiation pressure exerted on a specific target by an arbitrary acoustic wave in an infinite lossy medium was studied and a concise theoretical result was obtained. [The work was supported by grants CA 43920 and HL 41046 from the National Institutes of Health.]